The objectives of the project are to determine the factors responsible for regulation of intracellular cyclic adenosine 3', 5'-monophosphate (cAMP) and cyclic guanosine 3',5'-monophosphate (cGMP) content. The phosphodiesterases responsible for cyclic nucleotide hydrolysis were partially purified from rat liver. Three guanosine 3',5'-monophosphate phosphodiesterases were identified, partially purified, and their regulatory, structural and kinetic properties determined.